Association Between Pulmonary Vascular Remodeling And Expression Of Hypoxia Inducible Factor-1a Endothelin-1and Inducible Nitric Oxide Synthase In Pulmonary Vessels In Neonatal Rats With Hypoxic Pulmonary Hypertension

Objective:TO investigate the association between pulmonary vascular remod eling and expression of hypoxia-inducible factor-1a (HIF-1a), endothelin-1(ET-1) and inducible nitric oxide sythase (iNOS) in pulmonary vessels in neonatal ra ts with hypoxic pulmonary hypertension (HPH). Methods:A neonatal rat mod el of HPH was established as an HPH group, and normal neonatal rats were enr olled as a control group, The mean pulmonary arterial pressure (mPAP) was mea sured observe the ultrastructure of pulmonary vascular,The percentage of medial t hickness to outer diameter of the small pulmonary arteries (MT%) and the perce ntage of medial cross-section area to total cross-section area of the pulmonary s mall arteries (MA%) were measured as the indicators for pulmonary vascular em ondeling.The immunohistochemical reaction intensities for HIF-1α,ET-1,iNOS and their mRNAexpression in lung of neonatal rats were measured.Correlation analys is was performed to determine the relationship between pulmonary vascular remo deling andmRNA expression of HIF-1a,ET-land iNOS. Results:1) The mPAP of the HPH kept increasing on days3,5,7,10,14,and21of hypoxia,with a signifi cant differencecompared with the control group(P<0.05).2) ultrastructure demonstr ated that small pulmonary arterials became thicken,endothelial cell hyperplasia an d degeneration,and organelles increase in the HPH group after7days of hypoxia e xpourse,Besides collagen deposition in the extracelluar matrix and changes of pul monary vascular remodelling were observed.3)The HPH group had significantly hi gher MT%and MA%than the control group from day7of hypoxia(P<0.05).4) HIF-1a protein expression increased significantly on days3,5,7,10days of hyp oxia,and HIF-1a mRNA expression increased significantly on days3,5and7day s of hypoxia in the HPH group compared with the control group(P<0.05);ET-1protein expression increased significantly on days3,5and7days of hypoxia and ET-lmRNA expression increased significantly on day3of hypoxia in the HPH g roup compared with the group(P<0.05);Both iNOS protein and mRNA expression were significantly higher ondays3,5,7days of hypoxia than the control group(P <0.05);MT%and MA%were positively correlated with HIF-1a mRNA expressin (r=0.835and0.850repectively;P<0.05). Conclusions:Pulmonary vascular re modeling is developed onday7ofhypoxia in neonatal rats.HIF-1a,ET-1and iNOS are all involved in the occurrenceand development of HPH in neonatal rats.